World number two Naomi Osaka suffered a surprise third-round defeat to Swiss wildcard Jil Teichmann at the Cincinnati Masters.
The Japanese star, 23, lost 3-6 6-3 6-3 to the world number 76.
“I have high expectations of myself but there was nothing more I could do to win this match,” Osaka said.
Elsewhere, top seeds Daniil Medvedev and Ashleigh Barty are among the big names through to the quarter-finals in Cincinnati.
Russian world number two Medvedev beat Bulgaria’s Grigor Dimitrov 6-3 6-3 in the men’s draw.
He extends his winning streak to seven matches, having won the Canadian Open title on Sunday.
Meanwhile, British duo Andy Murray and Daniel Evans, who both exited the Cincinnati Masters earlier this week, have been given wildcards for the Winston-Salem Open – the final tournament before the start of the US Open on 30 August.
Murray was beaten in the second round by Hubert Hurkacz while British number one Evans lost to 10th seed Diego Schwartzman.
Reigning US and Australian Open champion Osaka, who lost in the third round at the recent Olympics in Tokyo, made 41 unforced errors in the match while hitting only 17 winners.
She was playing in her first tournament outside her homeland since withdrawing from the French Open in May.
The four-time Grand Slam winner went on to miss Wimbledon to take a break from tennis, having experienced anxiety and depression.
“I’m feeling more confident in myself,” said Osaka, who will look to defend her US Open title later this month. “There were times where I was doubting myself. It’s important to remind myself what my strengths are. I think I did that well in the first set.
“In the second set, maybe I played a bit more to her rhythm, and also in the third set, as well.”
Osaka will donate her $24,200 (£17,800) prize money in aid of the earthquake recovery effort in Haiti, her father’s homeland, with tournament officials matching her donation.
“I’m happy, but sad that I didn’t go further,” Osaka said. “But I think I raised awareness. I’m glad we were able to contribute something.”
Barty breezes through
Elsewhere in the women’s draw, Australia’s world number one and recent Wimbledon winner Barty stormed past Belarus’ defending champion Victoria Azarenka 6-0 6-2.
The Czech Republic’s Barbora Krejcikova beat Spain’s 2017 champion Garbine Muguruza 6-1 6-7 (5-7) 6-2, while Germany’s two-time Grand Slam champion Angelique Kerber is also through to the last eight, marking her 10th Cincinnati appearance with a 4-6 6-2 7-5 win over Latvia’s Jelena Ostapenko.
Czech 11th seed Petra Kvitova later defeated Tunisia’s Ons Jabeur 6-1 6-2.
In the men’s draw, German third seed Alexander Zverev progressed with a 6-2 6-3 win over Argentine Guido Pella, while Spain’s seventh seed Pablo Carreno Busta defeated ninth seed Hubert Hurkacz 7-6 (8-6) 7-6 (7-3) to set up a quarter-final clash with Medvedev.